Ethyl Acetate → HCID 11533851, compound

HRID 1983557Notes

Reaction equation

HRID 1983557 reaction equation
[CH2:1]([C:4]1[C:9]([OH:10])=[CH:8][N:7]=[C:6]2[N:11]([CH2:14][C:15]3[S:19][C:18]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=4)=[N:17][C:16]=3[CH2:30][CH2:31][CH2:32][CH3:33])[CH:12]=[CH:13][C:5]=12)[CH:2]=[CH2:3].C(=O)([O-])[O-].[Cs+].[Cs+].C([O:44][C:45](=[O:48])[CH2:46]Br)(C)(C)C.C(OCC)(=O)C>CN(C)C=O>[CH2:30]([C:16]1[N:17]=[C:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:28])([F:27])[F:29])=[CH:22][CH:21]=2)[S:19][C:15]=1[CH2:14][N:11]1[C:6]2=[N:7][CH:8]=[C:9]([O:10][CH2:46][C:45]([OH:48])=[O:44])[C:4]([CH2:1][CH2:2][CH3:3])=[C:5]2[CH:13]=[CH:12]1)[CH2:31][CH2:32][CH3:33]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 79177tert-Butyl bromoacetateHCID 57713029HCID 57713029, compound

Product 1

HCID 11533851HCID 11533851, compoundYield 44.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

140 mg 4-Allyl-1-[4-butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-1H-pyrrolo[2,3- b]pyridin-5-ol were dissolved in 10 ml dimethylformamide and 195 mg cesium carbonate and 116 mg tert.-butylbromoacetate were added. The reaction mixture was stirred at room temperature for two hours when 100 ml ethyl acetate were added and the mixture was washed five times with portions of 20 ml of water The organic layer was dried over MgSO4 and the solvent removed under reduced pressure. The residue was dissolved in 10 ml dichloromethane and 4 ml trifluoroacetic acid were added. The reaction mixture was stirred at room temperature for three hours then 100 ml toluene were added and the solvents removed under reduced pressure. The residue was dissolved in 20 ml methanol and 50 mg palladium (10% on charcoal) were added. The reaction mixture was stirred at room temperature in a hydrogen atmosphere (5 bar) for one hour. The catalyst was filtered off and the solvent removed under reduced pressure. The residue was purified by RP-HPLC to provide 70 mg {1-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-4-propyl-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-acetic acid as colorless lyophilisate.

Workup

  1. additionwere added
  2. washthe mixture was washed five times with portions of 20 ml of water The organic layer
  3. dry with materialwas dried over MgSO4
  4. customthe solvent removed under reduced pressure
  5. dissolutionThe residue was dissolved in 10 ml dichloromethane
  6. addition4 ml trifluoroacetic acid were added
  7. addition100 ml toluene were added
  8. customthe solvents removed under reduced pressure
  9. dissolutionThe residue was dissolved in 20 ml methanol
  10. addition50 mg palladium (10% on charcoal) were added
  11. stirringThe reaction mixture was stirred at room temperature in a hydrogen atmosphere (5 bar) for one hour
  12. filtrationThe catalyst was filtered off
  13. customthe solvent removed under reduced pressure
  14. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-6a6a1e8831464780856bc5dc4019cbc1
Source dataset
uspto-grants-2009_06
Patent number
US07541464B2

Reaction notes

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